Obesity constitutes a major human health problem that is growing in its importance. Most evidence suggests that variation in human obesity is best explained by complex multigenic inheritance. The central goal of this project is to identify genes controlling obesity in mice. A series of intercrosses involving inbred strains of mice will be studied to detect major genes influencing the development of obesity. Quantitative trait linkage analysis will be performed using linked markers to localize loci influencing quantitative variation in obesity phenotypes. To fine map each QTL, progeny tests will be performed on selected recombinant mice. In addition, chromosome segments containing obesity QTLs will be transferred to a C57BL/6J background to produce a set of congenic strains that differ by single obesity genes which can then be characterized physiologically. Candidate genes will be evaluated using genetic mapping and by functional analyses. The relative frequency of major obesity alleles will be examined among the parental inbred strains. The ultimate goal of this project is to identify (by positional cloning or candidate gene approaches) specific obesity genes.